Since AD progression is a spectrum with gradual changes starting from NC converting to MCI, characterizing (2-)connectedness of the brain FC networks at different stages could better help to understand how AD progression impacts the brain. Due to the findings that the brain FC network changes its topology to meet the moment-to-moment requirement for adaptive thinking and other high-order cognitive functions (e.g., attention and alertness) ([1]}, [2]}, [3]}, [4]}), we further assumed that the brain could be (2-)connected at different density levels in different period of time. Thus, we analyzed (2-)connectedness and their changes in brain dynamic FC networks. Specifically, we separately assessed connectedness and 2-connectedness of the time-varying FC networks with varied network densities to reveal the aforementioned critical points in a time-resolved manner in NC, MCI, and AD, with specific focuses on both the transitions from disconnected to connected states and those from connected to 2-connected states, and vice versa. Since AD is considered as a disconnected syndrome, we hypothesized that the connectedness status has been altered in AD versus NC and that the brain chronnectome in MCI might generally have more frequently increased redundancy as a compensatory effect to maintain normative cognitive abilities.
